Description

Strain Information

Type Mutant Stock; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   21-MAR-12 Species laboratory mouse Generation F?+F1 (15-JUL-11) Generation Definitions   Donating Investigator Brant R. Burkhardt,   University of South Florida

Description
Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR and Western blot analysis of pancreatic islets and small intestines from homozygotes. Male mice that are homozygous for the targeted mutation and 4 to 6 months of age exhibit higher blood glucose levels in glucose tolerance tests when compared to wildtype controls. Although, insulin sensitivity is normal in mutant mice, insulin levels are elevated after glucose stimulation (intraperitoneal glucose injection) due to decreased hepatic insulin clearance. Glucose intolerance is not observed in mutant female mice. Isolated pancreatic islets from male homozygotes have impaired glucose-stimulated insulin secretion and calcium signaling. Male homozygotes have reduced hepatic glucose production (HGP) and increased insulin-mediated HGP suppression conditions as determined by hyperinsulinemic-euglycemic clamp assays. Furthermore, male homozygotes display reduced expression of the critical gluconeogenic enzymes of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) following a 24 hour fast as compared to wildtype controls as determined by RT-PCR.

Development
A targeting vector containing a Neo selection cassette was used to disrupt the transcriptional start site (TSS), secretion signal peptide (SP), and exons 1 and 2. The construct was electroporated into 129S6/SvEvTac derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Heterozygotes were intercrossed to produce homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Fam3b^tm1Bkht allele

013788

B6.129S6-Fam3btm1Bkht/J

View Strains carrying   Fam3b^tm1Bkht     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Fam3b^tm1Bkht/Fam3b^tm1Bkht

        involves: 129S6/SvEvTac * C57BL/6

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • normal 24 and 48 hour fasting levels of glucose, insulin and glucagon   (MGI Ref ID J:167823)
• • abnormal glucose homeostasis
    • reduced hepatic glucose production during a hyperinsulinemic-euglycemic clamp   (MGI Ref ID J:167823)
  • • abnormal insulin clearance
      • impaired insulin clearance as indicated by a reduced C-peptide to insulin ratio   (MGI Ref ID J:167823)
    • decreased insulin secretion
      • decreased insulin secretion response by isolated islets exposed to increased glucose concentrations   (MGI Ref ID J:167823)
    • impaired glucose tolerance
      • male mice show higher blood glucose in glucose tolerance tests at 4 and 6 months of age   (MGI Ref ID J:167823)
      • glucose intolerance in 3 month old male mice   (MGI Ref ID J:167823)
    • increased circulating insulin level
      • elevated insulin after glucose injection   (MGI Ref ID J:167823)
• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype
  • normal islet architecture   (MGI Ref ID J:167823)
• • decreased insulin secretion
    • decreased insulin secretion response by isolated islets exposed to increased glucose concentrations   (MGI Ref ID J:167823)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Hyperglycemia
      males
Impaired Insulin Processing

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fam3btm1Bkht
Allele Name		targeted mutation 1, Brant Burkhardt
Allele Type		Targeted (knock-out)
Common Name(s)		PANDER-;
Mutation Made By		Brant Burkhardt,   University of South Florida
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Fam3b, family with sequence similarity 3, member B
Chromosome		16
Gene Common Name(s)		2-21; 9030624C24Rik; C21orf11; C21orf76; D16Jhu19e; DNA segment, Chr 16, Johns Hopkins University 19; DNA segment, Chr 16, Johns Hopkins University 19, expressed; ORF9; PANDER; RGD1311662; RIKEN cDNA 9030624C24 gene; open reading frame 9;
Molecular Note		Exons 1 and 2 were replaced with a neomycin selection cassette in reverse orientation. This removed the transcriptional and translational start sites and the first 54 amino acids including the secretion signal peptide and helix A. mRNA was not detectedin pancreatic islets, small intestine, liver, spleen, kidney, and brain by RT-PCR. Western blot analysis of pancratic islets demonstrated the absence of full length protein. [MGI Ref ID J:167823]

Genotyping

Genotyping Information

Genotyping Protocols

Fam3b^tm1Bkht, Standard PCR
Fam3b^tm1Bkht, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Robert-Cooperman CE; Carnegie JR; Wilson CG; Yang J; Cook JR; Wu J; Young RA; Wolf BA; Burkhardt BR. 2010. Targeted disruption of pancreatic-derived factor (PANDER, FAM3B) impairs pancreatic beta-cell function. Diabetes 59(9):2209-18. [PubMed: 20566664]  [MGI Ref ID J:167823]

Additional References

Fam3b^tm1Bkht related

Robert-Cooperman CE; Wilson CG; Burkhardt BR. 2011. PANDER KO mice on high-fat diet are glucose intolerant yet resistant to fasting hyperglycemia and hyperinsulinemia. FEBS Lett 585(9):1345-9. [PubMed: 21486565]  [MGI Ref ID J:171972]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   21-MAR-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101043 B6129SF1/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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